Supplement Alert! Carlson Labs Vitamin K2 MK-4 (Menatetrenone).

In 2003, I started supplementing with one a day of Ultra K2 Menatetrenone (MK-4) 15mg (plus 1.5g/day of Ca plus 400mg/day of Mg plus ~1,000iu/day of Vitamin D3) to reverse osteoporosis in my lumbar spine (bone density by DEXA went from -2SD to 0SD) in 3 years. I then used a maintenance dose of 15mg per week (~2,200ug per day). Everything was fine.

At some point, I switched to one a day of Vitacost Ultra Vitamin K with Advanced K2 Complex. Everything was fine.

Around 2012, I switched to one a day of Carlson Labs, Vitamin K2, 5 mg, in order to use-up my remaining iHerb rewards from the use of my discount code NIG935. I'd lost ~$300 of rewards through non-use. Everything was fine - for a while.

In ~2014, my right hip joint, which had previously caused me pain due to iliotibial band impingement on a bony/calcified outgrowth (cured when I began K2 supplementation), began to cause me pain again. As sleeping on my right side worsened the pain, I began to sleep on my left side. My GP felt my right hip joint and declared that there was some "wear & tear" in it and to use topical analgesics. This helped a bit.

In ~2015, my left shoulder joint, which had previously caused me pain due to impingement on a bony/calcified outgrowth (cured when I began K2 supplementation), began to cause me pain again. I assumed that it was "wear & tear", so I put up with it and applied topical analgesics. This helped a bit.

I recently looked-up rotator cuff pain and was perplexed to see that it was usually caused by impingement on a bony/calcified outgrowth. This of course is quite impossible, if taking 5mg/day of K2!

I took a look at the product reviews on iHerb.com, and noticed comments about joint pains from some reviewers, so I ordered a pot of Ultra K2 Menatetrenone (MK-4) 15mg.

Within a week of switching from Carlson Labs to Vitamin Research Products, my joint pains had virtually* all gone.

EDIT: The pain reduction was accompanied by a feeling of great relief and an increased tolerance to loud music & dazzling headlights. I think my cortisol level has dropped.

Therefore, there's something wrong with Carlson Labs, Vitamin K2, 5 mg. DO NOT USE!

*As the rotator cuff is damaged, there will always be some shoulder pain. As a herniated disk in my lumbar spine (before my osteoporosis was reversed) damaged nerves to/from my right leg, I walk lop-sidedly which means that there will always be some hip & knee joint pain.

Negative feedback loops, Tolerance, Dependence & Withdrawal.

I couldn't find the plot that I was looking for, but this electrical plot is equivalent.

From http://www.tpub.com/neets/book9/37k.htm

e_A represents the amount of a substance that perturbs one of the body's negative feedback loops. The amount oscillates between 0V & 100V.

e_R represents the effect of the substance on the body. 100V represents maximum effect and -100V represents maximum anti-effect.

The very first time that the substance is taken, there is 100V of effect, initially. As the time-constant of the negative feedback loop "kicks-in", the effect decays exponentially. Just before the substance is discontinued, the effect is down to 36.8V. Just after the substance is discontinued, the anti-effect is -63.2V. If the input continues to oscillate between 0V & 100V, the effect & anti-effect eventually become equal in magnitude. This is known as "cycling".

If the substance is applied continuously, the effect decays exponentially to 0V. When the substance is discontinued, the anti-effect is -100V initially, but decays exponentially to 0V.

This is analogous to drug tolerance, dependence & withdrawal, where eventually, the user has to take the drug just to feel normal, and discontinuing the drug gives the worst withdrawal symptoms ever, initially. After the drug has been discontinued for a while, the withdrawal symptoms decay exponentially to zero.

The above also applies to supplements that perturb one of the body's Hypothalamic Pituitary NFB loops e.g. the HPA (Adrenal), the HPG (Gonadal) or the HPT (Thyroid) Axes, or any other system (as everything in the body is regulated by a negative feedback loop).

This explains why a supplement can work really well at first, then its effect decays exponentially, until there is zero effect. The loop has compensated for it.

EDIT: If a loop is broken, due to zero secretion of one of the hormones controlling it, then a prescription drug/hormone restores the loop's output level to normal. E.g.

1) Prednisone for a broken HPAA (primary, secondary or tertiary hypoadrenalism) e.g. Addison's Disease.
2) Testosterone (men) or progesterone (women) for a broken HPGA (primary, secondary or tertiary hypogonadism).
3) Levothyroxine for a broken HPTA (primary, secondary or tertiary hypothyroidism) e.g. Hashimoto's thyroiditis.

I'm on 2) & 3), due to a broken pituitary gland. Luckily, it's not completely broken, so I don't need 1).

Rigid diets & taking loadsa supplements to compensate for them.

I do not believe you want to be doing that!

This post was inspired by a recently-published study by Alan Aragon & Brad Schoenfeld, as bodybuilders are a group of people who often eat a rigid diet (some eat skinless chicken breasts, broccoli & brown rice for several meals each day).

See Nutrient timing revisited: is there a post-exercise anabolic window?
"Collectively, these data indicate an increased potential for dietary flexibility while maintaining the pursuit of optimal timing."

This post is also aimed at people who eat severely restricted diets in the (often mistaken) belief that something's making them ill.

People with type 1 diabetes who struggle to keep their blood glucose within reasonable limits (3 to 8mmol/L, or 24 to 144mg/dL) benefit from restricting their intake of high-GL carbohydrates, so this post is not aimed at them. See The problem with Diabetes.

People with type 2 diabetes who severely restrict their intake of carbohydrates must be in caloric deficit, otherwise the physiological insulin resistance caused by high serum NEFAs will mess up just about everything in their body if they are in caloric balance or caloric excess. I've read (so it could be false) that a certain non-skinny blogger who I'm in conflict with (who has type 2 diabetes and who eats a VLC diet) has heart problems and is taking medication(s) for high blood pressure. Hmmm.

People who suffer from gastrointestinal problems after eating gluten-containing foods, or mucus after eating casein-containing foods may have impaired gut integrity. See Gluten - more than just a pain in the guts?

Supplements that I consider of positive value are:-

Fish oils: If the diet is low in oily fish (tinned tuna is not an oily fish), there may be insufficient EPA & DHA (especially in men, children & post-menopausal women). Women of reproductive age can get away with taking flaxseed oil.

Magnesium: If the diet is low in veg/high in dairy, there may be too much Calcium relative to Magnesium.

Vitamin D3: If the lifestyle results in sun-avoidance, insufficiency in Vitamin D is highly likely.

Vitamin K2: If the diet is low in animal fats and/or fermented foods, insufficiency in Vitamin K2 is highly likely.

Supplements that I consider of negative value are:-

Vitamin A: If there's an insufficiency in Vitamin D, supplementing with Vitamin A/β-carotene may exacerbate it. As Vitamin D + Calcium may reduce cancer risk, supplementing with Vitamin A absent Vitamin D3 may increase cancer risk.

Vitamin E: If there's an insufficiency in γ-tocopherol, supplementing with α-tocopherol may exacerbate it. As γ-tocopherol may reduce CHD mortality risk, supplementing with α-tocopherol absent γ-tocopherol may increase CHD mortality risk. Most Vitamin E supplements contain α-tocopherol only. Some Vitamin E supplements contain mixed tocopherols and these are O.K.

Is Coenzyme Q10 a supplement or a drug? It all depends.

This is the molecular structure of Coenzyme Q10.

Ubiquinone

I saw the following Tweet by Evelyn Kocur. Back in October 2009, a trial was started, to test the effect of CoQ10 supplementation on congestive heart failure (CHF). See Coenzyme Q10; an adjunctive therapy for congestive heart failure? See also Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of "Q-symbio"--a multinational trial.

The results of that trial have just been made public, but are not yet available on PubMed. See First Drug to Significantly Improve Heart Failure Mortality in Over a Decade. Wait, what? Back in 2009, it was a supplement. Now, because it works, it's a drug.

Supplementation in meaningful amounts of a substance that the body needs but lacks makes the body work better. Who knew?

Not exactly rocket science, is it? Part 2

If there is a deficiency in "X", taking supplement "X" will correct the deficiency in "X".
∴ If problem "Y" is caused by a deficiency in "X", taking supplement "X" will fix problem "Y".

If there's no deficiency in "X", taking supplement "X" won't make any difference.
∴ If problem "Y" isn't caused by a deficiency in "X", taking supplement "X" won't fix problem "Y".

If a person spends a lot of time outdoors in skimpy clothing in sun that's higher than 45deg in the sky, it's highly likely that they won't be deficient in Vitamin D3. Therefore, supplementing with 5,000iu/day of Vitamin D3 won't highly likely do anything.

∴ If the above sun-worshipping person has type 2 diabetes, supplementing with 5,000iu/day of Vitamin D3 won't highly likely make any difference.

Not exactly...

Rocket Science!

There will be some people for whom all of the supplements & exercises that I recommend don't make any difference to their type 2 diabetes. Sorry about that. A low-carb (but not very-low-carb) diet will minimise your serum glucose level fluctuations without increasing your serum NEFA level excessively. See The problem with Diabetes.

Can supplements & exercise cure Type 2 diabetes?

Definitely, maybe!

From http://health-in-hand.co.uk/2013/03/24/supplements-for-the-non-supplement-takers/

According to Hyppönen and Power, in a large sample of the white British population born in 1958, 60.9% of subjects had serum 25(OH)D (the active metabolite of Vitamin D) of less than 75nmol/L in Summer & Autumn, and 87.1% had serum 25(OH)D of less than 75nmol/L in Winter & Spring. 75nmol/L ≡ 30ng/mL.

 From Hypovitaminosis D is associated with insulin resistance and β cell dysfunction, 2-hour post-load blood glucose level in an oral glucose tolerance test (OGTT) has a negative correlation with 25(OH)D concentration (Fig 1C). 25(OH)D concentration has a positive correlation with insulin sensitivity (Fig 2A). Therefore, 2-hour post-load blood glucose level in a OGTT has a negative correlation with insulin sensitivity.

"Extrapolation from the observations in the current study suggests that increasing 25(OH)D from 10 to 30 ng/mL can improve insulin sensitivity by 60%, from 3.8128 to 6.1176 (umol/L)·m-2·min-1·(pmol/L)-1. This improvement in insulin resistance could potentially eliminate the burden on cells and reverse abnormal glucose tolerance. Furthermore, the 60% improvement in insulin sensitivity that results from vitamin D treatment indicates that that treatment is more potent than either troglitazone or metformin treatment (54% and 13% improvement in insulin sensitivity, respectively). The modest effect of vitamin D on insulin sensitivity in individual persons may translate into a dramatic effect in the population as a whole because of the high prevalence of hypovitaminosis D, which, in a large population, carries an attributable risk for type 2 diabetes and the metabolic syndrome. Although a review of the literature suggests non-calcium-mediated effects, the underlying molecular mechanism remains to be elucidated."

As my 2-hour post-load blood glucose level in a OGTT became low (3.7mmol/L, from 8.7mmol/L in 2003) after supplementing with 5,000iu/day of Vitamin D3, this means that my insulin sensitivity became high. Therefore, I cured my pre-type 2 diabetes using supplements.

My fasting blood glucose level also fell from 6.8 mmol/L (> 7.0mmol/L = type 2 diabetes diagnosis) to 5.0mmol/L. I achieved this without taking any drugs for type 2 diabetes - not even Metformin, which I consider to be a safe & effective insulin-sensitiser, though it can cause gastric distress and B12 absorption issues, long-term. The supplements that I took had zero side-effects and merely corrected deficiencies.

Diabetes drugs cannot cure type 2 diabetes. However, supplements & exercise can cure type 2 diabetes, if the type 2 diabetes is caused by nutrient deficiencies and/or sedentary behaviour and if all pancreatic beta cells haven't been destroyed. Insulin injections can preserve pancreatic beta cells, while insulin resistance is being tackled. See Dr. Richard K Bernstein on insulin for type 2 diabetics, and some definitions.

Sadly, if there are no nutrient deficiencies and/or all pancreatic beta cells have been destroyed, supplements & exercise will not help.

Quality >> Quantity.

Mum passed away peacefully in the middle of the night. I'm waiting for paperwork to be done.

"And the best you can hope for is to die in your sleep."

On the internet, I read that Dementia with Lewy bodies has a mean survival time of 6 years from the onset of symptoms. Mum first became confused in mid-July 2007, so it's been just under 6 years. Does this mean that all of the supplements I gave her were worthless. Hell, no!

As mentioned in Look after your brain., mum's MMSE score increased from 14 to 26 out of 30 after taking medication and supplements. The medication gave a 3 point increase in MMSE score on average, so the rest of the increase in MMSE score was probably due to the supplements, which had no undesirable side-effects.

On Christmas day 2008, mum was capable of preparing Brussels sprouts for cooking, though she got the knives, forks & spoons mixed up when she tried to lay the table. Here's her final Christmas at home. Roast duck with all of the trimmings. Om, nom, nom!

Mum's last Christmas at home.

People commented on how happy mum always was. Even though she probably didn't know who she was or I was, when I said "Fancy a cup of tea, mum?", she'd reply "Ooh yes, please!" That was the last part of her speech to go.

In conclusion, I believe that quality of life trumps quantity of life, so supplementation for the win.

Everyone is Different, Part 3.

Cont'd from Everyone is Different, Part 2.

Hat-tip to Bill Lagakos, whose article Missing: 300 kilocalories reminded me of the following graphic from Effects of Dietary Composition During Weight Loss Maintenance: A Controlled Feeding Study.

Lo and behold, even when subjects are bribed to stick to the diets that they are provided with, the effect of eating those diets varies hugely.

So, people like ItsTheWoo and Petro Dobromylskyj (yes, I have to copy and paste the name from his site every freakin' time!) rave about how awful carbs are, while people like Go Kaleo and Matt Stone rave about how awesome carbs are.

Everyone is different for a number of reasons, some of which are unchangeable and some of which are changeable. We can't change our birth weight, what our mums ate when we were in the womb or the chemicals that we were exposed to in the past. We can't change our genes, but we can change the expression of our genes by changing diet, activity and even supplementation. See Influence of Vitamin D Status and Vitamin D₃ Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial.

Continued on Bray et al shows that a calorie *is* a calorie (where weight is concerned)

Supplements: Who needs 'em?

According to Health Professionals, nobody. Apparently, we get all of the vitamins, minerals & other nutrients that we need from a "Healthy Balanced Diet" (whatever that is!).

According to me, just about everybody. Due to modern farming methods, food ain't what it used to be. Dammit, even nostalgia ain't what it used to be! Due to changes in lifestyle:-

a) People are more sedentary than they used to be. This means that they require less food than they used to in order to not get fat. Less food, coupled with less nutrients in the food = dietary deficiencies.

b) People don't get as much sun on their skin as they used to, as they now work, play & live mostly indoors and when they do go outside, they are encouraged to Slip Slop Slap (slip on a shirt, slop on sunscreen and slap on a hat). This results in hypovitaminosis D, as only an Eskimo's diet contains enough dietary Vitamin D. The RDA of 200/400/600iu/day (depending on age) is woefully inadequate and totally out of touch with modern research.

c) Many people don't eat much oily fish. Also, animal & vegetable produce now contains more omega-6 & less omega-3 than it used to. This can result in a large imbalance. I eat two 120g cans of mackerel in spicy sauce a day. This also provides protein.

d) Diets low in dark green vegetables & fruits lack Magnesium & Potassium.

e) Diets low in fermented foods lack Vitamin K2.

I currently supplement with:-
400mg/day of Magnesium, as 4g/day Epsom Salts dissolved in water & the solution added to drinks.
5,000iu/day of Vitamin D3.
15mg/day of Vitamin K2.

See also The usual suspects.